The metabolism of pronethalol

Pronethalol is metabolised by two main pathways, side chain oxidation, and ring hydroxylation and conjugation. Five metabolites have been identified by comparison with synthetic substances. Four of these, 2-amino-1-(2-naphthyl)ethanol, 2-naphthylglycollic acid, 2-naphthylglyoxylic acid, and 2-naphthoic acid are formed by degradation of the isopropylaminoethanol side chain. The fifth, the 7-hydroxy-analogue of pronethalol, is partly present in the free form, but the major amount is present as a glucuronide in which the glucuronic acid residue is attached to the phenolic hydroxyl group. In several species of animals, and in humans, the differences in the major metabolites are of a quantitative rather than a qualitative nature. We have been unable to determine the nature of the proximate carcinogen responsible for producing thymic tumours in mice, but it is unlikely to be one of the major metabolites. The 7-hydroxy-analogue of pronethalol is about five times more potent than pronethalol as a β-adrenergic blocking agent and is probably responsible for some, but not all, the pharmacological activity of pronethalol.